title: Regulation of the heme A biosynthetic pathway: differential regulation of heme A synthase and heme O synthase in Saccharomyces cerevisiae.
abstract: The assembly and activity of cytochrome c oxidase is dependent on the availability of heme A, one of its essential cofactors. In eukaryotes, two inner mitochondrial membrane proteins, heme O synthase (Cox10) and heme A synthase (Cox15), are required for heme A biosynthesis. In this report, we demonstrate that in Saccharomyces cerevisiae the transcription of COX15 is regulated by Hap1, a transcription factor whose activity is positively controlled by intracellular heme concentration. Conversely, COX10, the physiological partner of COX15, does not share the same regulatory mechanism with COX15. Interestingly, protein quantification identified an 8:1 protein ratio between Cox15 and Cox10. Together, these results suggest that heme A synthase and/or heme O synthase might play a new, unidentified role in addition to heme A biosynthesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, 48823, USA.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Wang
authors.forename: Eric L
authors.initials: EL
authors.lastname: Hegg
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D006418:Heme / Q000031:analogs & derivatives* / Q000096:biosynthesis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
chemical_list: C107633:COX15 protein, S cerevisiae; D004268:DNA-Binding Proteins; C058452:HAP1 protein, S cerevisiae; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C027728:heme a; D006418:Heme; D003576:Electron Transport Complex IV; D019883:Alkyl and Aryl Transferases; C086105:COX10 protein, S cerevisiae